ACTA PHYSIOLOGICA, Issue 2 2002
F. R. IBARRA
ABSTRACT The natriuretic hormone dopamine and the antinatriuretic hormone noradrenaline, acting on , -adrenergic receptors, have been shown to bidirectionally modulate the activity of renal tubular Na+,K+ -adenosine triphosphate (ATPase). Here we have examined whether intracellular sodium concentration influences the effects of these bidirectional forces on the state of phosphorylation of Na+,K+ -ATPase. Proximal tubules dissected from rat kidney were incubated with dopamine or the , -adrenergic agonist, oxymetazoline, and transiently permeabilized in a medium where sodium concentration ranged between 5 and 70 mM. The variations of sodium concentration in the medium had a proportional effect on intracellular sodium. Dopamine and protein kinase C (PKC) phosphorylate the catalytic subunit of rat Na+,K+ -ATPase on the Ser23 residue. The level of PKC induced Na+,K+ -ATPase phosphorylation was determined using an antibody that only recognizes Na+,K+ -ATPase, which is not phosphorylated on its PKC site. Under basal conditions Na+,K+ -ATPase was predominantly in its phosphorylated state. When intracellular sodium was increased, Na+,K+ -ATPase was predominantly in its dephosphorylated state. Phosphorylation of Na+,K+ -ATPase by dopamine was most pronounced when intracellular sodium was high, and dephosphorylation by oxymetazoline was most pronounced when intracellular sodium was low. The oxymetazoline effect was mimicked by the calcium ionophore A23187. An inhibitor of the calcium-dependent protein phosphatase, calcineurin, increased the state of Na+,K+ -ATPase phosphorylation. The results imply that phosphorylation of renal Na+,K+ -ATPase activity is modulated by the level of intracellular sodium and that this effect involves PKC and calcium signalling pathways. The findings may have implication for the regulation of salt excretion and sodium homeostasis. [source]

Gap junctional coupling between progenitor cells at the retinal margin of adult goldfish

DEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001
Fuminobu Tamalu
Abstract We prepared living slice preparations of the peripheral retina of adult goldfish to examine electrical membrane properties of progenitor cells at the retinal margin. Cells were voltage-clamped near resting potential and then stepped to either hyperpolarizing or depolarizing test potentials using whole-cell voltage-clamp recordings. Electrophysiologically examined cells were morphologically identified by injecting both Lucifer Yellow (LY) and biocytin. All progenitor cells examined (n = 37) showed a large amount of passively flowing currents of either sign under suppression of the nonjunctional currents flowing through K+ and Ca2+ channels in the cell membrane. They did not exhibit any voltage-gated Na+ currents. Cells identified by LY fills were typically slender. As the difference between the test potential and the resting potential increased, 13 out of 37 cells exhibited symmetrically voltage- and time-dependent current decline on either sign at the resting potential. The symmetric current profile suggests that the current may be driven and modulated by the junctional potential difference between the clamping cell and its neighbors. The remaining 24 cells did not exhibit voltage dependency. A gap junction channel blocker, halothane, suppressed the currents. A decrease in extracellular pH reduced coupling currents and its increase enhanced them. Dopamine, cAMP, and retinoic acid did not influence coupling currents. Injection of biocytin into single progenitor cells revealed strong tracer coupling, which was restricted in the marginal region. Immature ganglion cells closely located to the retinal margin exhibited voltage-gated Na+ currents. They did not reveal apparent tracer coupling. These results demonstrate that the marginal progenitor cells couple with each other via gap junctions, and communicate biochemical molecules, which may subserve or interfere with cellular differentiation. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 204,214, 2001 [source]

Dopamine and sensory tissue development in Drosophila melanogaster

DEVELOPMENTAL NEUROBIOLOGY, Issue 4 2001
Wendi Neckameyer
Abstract Dopamine is an important signaling molecule in the nervous system; it also plays a vital role in the development of diverse non-neuronal tissues in the fruit fly Drosophila melanogaster. The current study demonstrates that males depleted of dopamine as third instar larvae (via inhibition of the biosynthetic enzyme tyrosine hydroxylase) demonstrated abnormalities in courtship behavior as adults. These defects were suggestive of abnormalities in sensory perception and/or processing. Electroretinograms (ERGs) of eyes from adults depleted of dopamine for 1 day as third instar larvae revealed diminished or absent on- and off-transients. These sensory defects were rescued by the addition of L -DOPA in conjunction with tyrosine hydroxylase inhibition during the larval stage. Depletion of dopamine in the first or second larval instar was lethal, but this was not due to a general inhibition of proliferative cells. To establish that dopamine was synthesized in tissues destined to become part of the adult sensory apparatus, transgenic lines were generated containing 1 or 4 kb of 5, upstream sequences from the Drosophila tyrosine hydroxylase gene (DTH) fused to the E. coli ,-galactosidase reporter. The DTH promoters directed expression of the reporter gene in discrete and consistent patterns within the imaginal discs, in addition to the expected expression in gonadal, brain, and cuticular tissues. The ,-galactosidase expression colocalized with tyrosine hydroxylase protein. These results are consistent with a developmental requirement for dopamine in the normal physiology of adult sensory tissues. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 280,294, 2001 [source]

The Influence of the Cathodic Pretreatment on the Electrochemical Detection of Dopamine by Poly(1-aminoanthracene) Modified Electrode

ELECTROANALYSIS, Issue 19 2010
Estela de Pieri Troiani
Abstract In this study we demonstrated the influence of the cathodic pretreatment of poly(1-aminoanthracene) (PAA) electropolymerized on a platinum electrode for determination of dopamine (DA). The DA electrochemical response was obtained after a cathodic pretreatment of the PAA electrode which consisted of applying a potential of ,0.7,V (vs. Ag/AgCl) for 3,s before each measurement. The pretreatment of the electrode changed the PAA electrocatalytic properties so that the electrode began to present electrochemical response to DA without interference of ascorbic acid (AA). The anodic peak currents determined by differential pulse voltammetry using pretreated PAA showed a linear dependence on the DA concentration from 0.56 to 100,µM with a detection limit of 0.13,µM and a correlation coefficient of 0.9986. The electrode exhibits a relative standard deviation of 1.2,% for ten successive measurements of a 0.5,mM DA solution. The analysis by scanning electron microscopy and atomic force microscopy show a homogeneous and nanostructured film with globular structures with diameter of about 20,nm. The analytical results obtained for DA determination at a pretreated PAA electrode in pharmaceutical formulation sample were in good agreement with those obtained by a comparative procedure at a 95,% confidence level. PAA electrode after the pretreatment showed electrochemical responses to DA with excellent selectivity, sensitivity, and high stability without interference of AA. [source]

Simultaneous Determination of Ascorbic Acid, Dopamine and Uric Acid at Pt Nanoparticles Decorated Multiwall Carbon Nanotubes Modified GCE

ELECTROANALYSIS, Issue 10 2010
Zekerya Dursun
Abstract A modified electrode was fabricated by electrochemically deposition of Pt nanoparticles on the multiwall carbon nanotube covered glassy carbon electrode (Pt nanoparticles decorated MWCNT/GCE). A higher catalytic activity was obtained to electrocatalytic oxidation of ascorbic acid, dopamine, and uric acid due to the enhanced peak current and well-defined peak separations compared with both, bare and MWCNT/GCE. The electrode surfaces were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and electrochemical impedance spectroscopy (EIS). Individual and simultaneous determination of AA, DA, and UA were studied by differential pulse voltammetry. The detection limits were individually calculated for ascorbic acid, dopamine, and uric acid as being 1.9×10,5,M, 2.78×10,8,M, and 3.2×10,8,M, respectively. In simultaneous determination, LODs were calculated for AA, DA, and UA, as of 2×10,5,M, 4.83×10,8,M, and 3.5×10,7,M, respectively. [source]

Silver Doped Poly(L -valine) Modified Glassy Carbon Electrode for the Simultaneous Determination of Uric Acid, Ascorbic Acid and Dopamine

ELECTROANALYSIS, Issue 5 2010
Wenna Hu
Abstract In this paper, a silver doped poly(L -valine) (Ag-PLV) modified glassy carbon electrode (GCE) was fabricated through electrochemical immobilization and was used to electrochemically detect uric acid (UA), dopamine (DA) and ascorbic acid (AA) by linear sweep voltammetry. In pH,4.0 PBS, at a scan rate of 100,mV/s, the modified electrode gave three separated oxidation peaks at 591,mV, 399,mV and 161,mV for UA, DA and AA, respectively. The peak potential differences were 238,mV and 192,mV. The electrochemical behaviors of them at the modified electrode were explored in detail with cyclic voltammetry. Under the optimum conditions, the linear ranges were 3.0×10,7 to 1.0×10,5,M for UA, 5.0×10,7 to 1.0×10,5,M for DA and 1.0×10,5 to 1.0×10,3,M for AA, respectively. The method was successfully applied for simultaneous determination of UA, DA and AA in human urine samples. [source]

Simultaneous Determination of Dopamine and Ascorbic Acid Using the Nano-Gold Self-Assembled Glassy Carbon Electrode

ELECTROANALYSIS, Issue 10 2009
Guangzhi Hu
Abstract Electrochemical behavior of dopamine (DA) was investigated at the gold nanoparticles self-assembled glassy carbon electrode (GNP/LC/GCE), which was fabricated by self-assembling gold nanoparticles on the surface of L -cysteine (LC) modified glassy carbon electrode (GCE) via successive cyclic voltammetry (CV). A pair of well-defined redox peaks of DA on the GNP/LC/GCE was obtained at Epa=0.197,V and Epc=0.146,V, respectively. And the peak separation between DA and AA is about 0.2,V, which is enough for simultaneous determination of DA and AA. The peak currents of DA and AA were proportional with their concentrations in the range of 6.0×10,8,8.5×10,5 mol L,1 and 1.0×10,6,2.5×10,3 mol L,1, with the detection limit of 2.0×10,8 mol L,1 and 3.0×10,7 mol L,1 (S/N=3), respectively. The modified electrode exhibits an excellent reproducibility, sensibility and stability for simultaneous determination of DA and AA in human serum with satisfactory result. [source]

Some Properties of Sodium Dodecyl Sulfate Functionalized Multiwalled Carbon Nanotubes Electrode and Its Application on Detection of Dopamine in the Presence of Ascorbic Acid

ELECTROANALYSIS, Issue 16 2008
Dan Zheng
Abstract A sodium dodecyl sulfate (SDS) functionalized multiwalled carbon nanotubes (MWNTs) electrode (SDS/MWNTs) was successfully constructed in this study. The electrochemical property of the SDS/MWNTs electrode has been characterized by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Nyquist plots suggest that the immersion time of SDS affects the resistances of the MWNTs electrodes. The thickness of adsorbed SDS on MWNTs surface is estimated to be 1.23,nm, which is close to the value of SDS monolayer. CV results demonstrate a 5-fold enhanced response for dopamine (DA) at the SDS/MWNTs electrode compared to the bare MWNTs one. DPV results illustrate that DA can be selectively determined in the presence of high concentration ascorbic acid (AA) with a linear range from 20,,M to 0.20,mM and a sensitivity of 0.024,,A ,M,1 at the SDS/MWNTs electrode. [source]

Selective Determination of Dopamine in the Presence of Ascorbic Acid at Porous-Carbon-Modified Glassy Carbon Electrodes

ELECTROANALYSIS, Issue 11 2008
Shuqing Song
Abstract Selective dopamine (DA) determinations using porous-carbon-modified glassy carbon electrodes (GCE) in the presence of ascorbic acid (AA) were studied. The effects of structure textures and surface functional groups of the porous carbons on the electrochemical behavior of DA was analyzed based on both cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements. The differential pulse voltammetry of DA on the modified GCE was determined in the presence of 400-fold excess of AA, and the linear determination ranges of 0.05,0.99, 0.20,1.96, and 0.6,12.60,,M with the lowest detected concentrations of 4.5×10,3, 4.4×10,2, and 0.33,,M were obtained on the mesoporous carbon, mesoporous carbon with carboxylic and amino groups modified electrodes, respectively. [source]

Electrochemical Characterization of In Situ Functionalized Gold Cysteamine Self-Assembled Monolayer with 4-Formylphenylboronic Acid for Detection of Dopamine

ELECTROANALYSIS, Issue 5 2008
Karimi Shervedani
Abstract Functionalization of gold cysteamine (AuCA) self-assembled monolayer with 4-formylphenylboronic acid (BA) via Schiff's base formation, through in situ method to fabricate Au-CA-BA electrode is presented and described. The fabricated electrode was used as a novel sensor for accumulation and determination of dopamine (DA). The accumulation of DA as a diol on the topside of Au-CA-BA as a Lewis acid, was performed via esterification (AuCABADA), and followed for determination of DA. Functionalization, characterization, and determination steps were probed by electrochemical methods like cyclic voltammetry and electrochemical impedance spectroscopy. The data will be presented and discussed from which a new sensor for DA is introduced. [source]

Chitosan Incorporating Cetyltrimethylammonium Bromide Modified Glassy Carbon Electrode for Simultaneous Determination of Ascorbic Acid and Dopamine

ELECTROANALYSIS, Issue 17 2007
Xuelian Zou
Abstract Simultaneous determination of a neurotransmitter, dopamine (DA), and ascorbic acid (AA) is achieved at neutral pH on a chitosan incorporating cetyltrimethylammonium bromide (CTAB) modified glassy carbon (GC) electrode. Differential pulse voltammetry (DPV) technique was used to investigate the electrochemical response of DA and AA at a glassy carbon electrode modified with chitosan incorporating CTAB. An optimum 6.0,mmol L,1 of CTAB together with 0.5 wt% of chitosan was used to improve the resolution and the determination sensitivity. In 0.1,mol L,1 aqueous phosphate buffer solution of pH,6.8, the chitosan-CTAB modified electrode showed a good electrocatalytic response towards DA and AA. The anodic peak potential of DA shifted positively, while that of AA shifted negatively. Thus, the difference of the anodic peaks of DA and AA reached 0.23,V, which was enough to separate the two anodic peaks very well. The presented method herein could be applied to the direct simultaneous determination of DA and AA without prior treatment. The anodic peak currents (Ipa) of DPV are proportional to DA in the concentration range of 8,,M to 1000,,M, to that of AA 10,,M to 2000,,M, with correlation coefficients of 0.9930 and 0.9945, respectively. The linear range is much wider than previously reported. [source]

Electrochemical Preparation of Poly(Malachite Green) Film Modified Nafion-Coated Glassy Carbon Electrode and Its Electrocatalytic Behavior Towards NADH, Dopamine and Ascorbic Acid

ELECTROANALYSIS, Issue 14 2007
Shen-Ming Chen
Abstract Poly(malachite green) film modified Nafion-coated glassy carbon electrodes have been prepared by potentiodynamic cycling in malachite green solution. The pH of polymerisation solution has only minor effect on film formation. Electrochemical quartz crystal microbalance (EQCM) was used to monitor the growth of the poly(malachite green) film. Cyclic voltammogram of the poly(malachite green) film shows a redox couple with well-defined peaks. The redox response of the modified electrode was found to be depending on the pH of the contacting solution. The peak potentials were shifted to a less positive region with increasing pH and the dependence of the peak potential was found to be 56,mV per pH unit. The electrocatalytic behavior of poly(malachite green) film modified Nafion-coated glassy carbon electrodes was tested towards oxidation of NADH, dopamine, and ascorbic acid. The oxidation of dopamine and ascorbic acid occurred at less positive potential on poly(malachite green) film compared to bare glassy carbon electrode. In the case of NADH, the overpotential was reduced substantially on modified electrode. Finally, the feasibility of utilizing poly(malachite green) film electrode in analytical estimation of ascorbic acid was demonstrated in flow injection analysis. [source]

Electrocatalysis and Voltammetric Determination of Dopamine at a Calix[4]arene Crown-4 Ether Modified Glassy Carbon Electrode

ELECTROANALYSIS, Issue 4 2007
Guo-Song Lai
Abstract A sensitive and selective electrochemical method for the determination of dopamine (DA) was developed using a calix[4]arene crown-4 ether (CACE) film modified glassy carbon electrode (GCE). The modified electrode exhibited good electrocatalytic activity for electrochemical oxidation of DA in the pH,6.00 Britton,Robinson buffer solution, and ascorbic acid (AA) did not interfere with it. The diffusion coefficient (D=2.7×10,5,cm2 s,1), and the kinetic parameter such as the electron transfer coefficient (,=0.54) of DA at the surface of CACE were determined using electrochemical approaches. The catalytic oxidation peak currents showed a linear dependence on the DA concentration and a linear analytical curve was obtained in the range of 2.0×10,5,1.0×10,3,M of DA with a correlation coefficient of 0.9990. The detection limit (S/N=3) was estimated to be 3.4×10,6,M. This method was also examined for the determination of DA in an injection sample. In addition, effects of possible interferences were investigated. The present work shows the potential of the proposed method for the fabrication of a modified electrode, as it can be effectively used for voltammetric detection of DA. [source]

The Electrochemical Properties of Co(TPP), Tetraphenylborate Modified Glassy Carbon Electrode: Application to Dopamine and Uric Acid Analysis

ELECTROANALYSIS, Issue 5 2006
Yunlong Zeng
Abstract We report the combination of the charge repelling property of tetraphenyl-borate (TPB) anion and the electrooxidation catalytic effect of cobalt(II) tetrakisphenylporphyrin (CoTPP) embedded in a sol gel ceramic film to develop a modified glassy carbon electrode (CoTPP-TPB-SGGCE) for the simultaneous determination of dopamine (DA) and uric acid (UA). The optimized CoTPP-TPB-SGGCE shows excellent sensitivity and selectivity for the DA and UA analysis. As high as 2000 fold acceptable tolerance of ascorbic acid (AA) for the determination of trace DA and UA is reached. In the presence of 0.10,mM AA, the linear concentration range for DA is from 6.0×10,8 to 2.5×10,5,M, and the detection limit is 2.0×10,8,M. For UA, the linear concentration range is from 1.0×10,7 to 3.5×10,5,M, and the detection limit is 7.0×10,8,M. Our study has also demonstrated that the novel CoTPP-TPB-SGGCE shows high stability and reliability. For 6.00,,M DA and UA, a total of 12,measurements were taken in one week, and the relative standard deviation is 2.05% and 2.68% respectively. No obvious shift of peak current and peak potential is observed over a three-month lifetime test. The response of the sensor is very quick and response time is approximately 1,s. Satisfactory results are also achieved when the CoTPP-TPB-SGGCEs being used to detect the DA and UA in human urine samples. [source]

A LiMn2O4 Based Electrochemical Scheme for Selective Measurement of Dopamine

ELECTROANALYSIS, Issue 3 2006
Hoang, Jyh Leu
Abstract A new cathodic scheme was developed for the determination of dopamine by flow injection analysis (FIA). A mild oxidizing agent, lithium manganese (III, IV) oxide (LiMn2O4), as an upstream modifier can oxidize the dopamine to produce the dopaminequinone, and then the oxidized product is subsequently detected by the downstream detector at ,0.1,V (vs. Ag/AgCl). In this work, the significant feature of LiMn2O4 based sensing scheme possesses no interference from other tested biological amines including acetylcholine, epinephrine, glutamate, and histamine. Otherwise, there is no detectable interference from ascorbic acid, but 2% and 1% negligible interferences were found from uric acid and acetaminophen, respectively. [source]

Electrochemical Behavior and Detection of Dopamine and Ascorbic Acid at an Iron(II)tetrasulfophthalocyanine Modified Carbon Paste Microelectrode

ELECTROANALYSIS, Issue 10 2003
Joshua Oni
Abstract In this article the electrocatalytic behavior of an iron(II)tetrasulfophthalocyanine modified carbon paste microelectrode for the oxidation of dopamine (DA) and ascorbic acid (AA) is described. Although the oxidation potential of ascorbic acid is shifted by over 100,mV to more positive potentials, no peak separation could be obtained. This can be explained by the immediate homogeneous reduction of the oxidation product of dopamine by ascorbic acid in solution. However, this reaction induces a shift of the half-wave potential as a function of ratio of concentration of dopamine to ascorbic acid (cDA/cAA). Therefore it was possible to determine the cAA and cDA from this potential shift and the experimental peak current. Detection limits of 4.5±0.2×10,7 and 7.5±0.5×10,7,mol,L,1 were obtained respectively for dopamine and ascorbic acid for cDA/cAA>0.01. [source]

Role of peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity and sensitization in mice

ADDICTION BIOLOGY, Issue 3 2000
Syed F. Ali
Methamphetamine (METH)-induced dopaminergic neurotoxicity is thought to be associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recently, we have reported that copper/zinc(CuZn)-superoxide dismutase transgenic mice are resistant to METH-induced neurotoxicity. In the present study, we examined the role of the neuronal nitric oxide synthase (nNOS), susceptibility of nNOS knockout (KO) mice and sensitization to psychostimulants after neurotoxic doses of METH. Male SwissWebster mice were treated with or without 7-nitroindazole (7-NI) along with METH (5 mg/kg,ip,q 3h × 3) and were sacrificed 72 h after the last METH injection. Dopamine (DA) and dopamine transporter (DAT) binding sites were determined in striatum from saline and METH-treated animals. 7-NI completely protected against the depletion of DA, and DAT in striatum. In follow-up experiments nNOS KO mice along with appropriate control (C57BL/6N, SV129 and B6JSV129) mice were treated with METH (5 mg/kg,ip, q 3h × 3) and were sacrificed 72 h after dosing. This schedule of METH administrations resulted in only 10,20% decrease in tissue content of DA and no apparent change in the number of DAT binding sites in nNOS KO mice. However, this regime of METH resulted in a significant decrease in the content of DA as well as DAT binding sites in the wild-type animals. Pre-exposure to single or multiple doses of METH resulted in a marked locomotion sensitization in response to METH. However, the nNOS KO mice show no sensitization in response to METH after single or multiple injections of METH. Therefore, these studies strongly suggest the role of peroxynitrite, nNOS and DA system in METH-induced neurotoxicity and behavioral sensitization. [source]

Dopamine modulation of excitatory currents in the striatum is dictated by the expression of D1 or D2 receptors and modified by endocannabinoids

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2010
Véronique M. André
Abstract Striatal medium-sized spiny neurons (MSSNs) receive glutamatergic inputs modulated presynaptically and postsynaptically by dopamine. Mice expressing the gene for enhanced green fluorescent protein as a reporter gene to identify MSSNs containing D1 or D2 receptor subtypes were used to examine dopamine modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in slices and postsynaptic N -methyl- d -aspartate (NMDA) and ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) currents in acutely isolated cells. The results demonstrated dopamine receptor-specific modulation of sEPSCs. Dopamine and D1 agonists increased sEPSC frequency in D1 receptor-expressing MSSNs (D1 cells), whereas dopamine and D2 agonists decreased sEPSC frequency in D2 receptor-expressing MSSNs (D2 cells). These effects were fully (D1 cells) or partially (D2 cells) mediated through retrograde signaling via endocannabinoids. A cannabinoid 1 receptor (CB1R) agonist and a blocker of anandamide transporter prevented the D1 receptor-mediated increase in sEPSC frequency in D1 cells, whereas a CB1R antagonist partially blocked the decrease in sEPSC frequency in D2 cells. At the postsynaptic level, low concentrations of a D1 receptor agonist consistently increased NMDA and AMPA currents in acutely isolated D1 cells, whereas a D2 receptor agonist decreased these currents in acutely isolated D2 cells. These results show that both glutamate release and postsynaptic excitatory currents are regulated in opposite directions by activation of D1 or D2 receptors. The direction of this regulation is also specific to D1 and D2 cells. We suggest that activation of postsynaptic dopamine receptors controls endocannabinoid mobilization, acting on presynaptic CB1Rs, thus modulating glutamate release differently in glutamate terminals projecting to D1 and D2 cells. [source]

Effects of dopamine-related gene,gene interactions on working memory component processes

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2009
Christine Stelzel
Abstract Dopamine modulates complex cognitive functions like working memory and cognitive control. It is widely accepted that an optimal level of prefrontal dopamine supports working memory performance. In the present study we used a molecular genetic approach to test whether the optimal activity of the dopamine system for different component processes of working memory is additionally related to the availability of dopamine D2 receptors. We sought evidence for this assumption by investigating the interaction effect (epistasis) of variations in two dopaminergic candidate genes: the catechol- O -methyltransferase (COMT) Val158Met polymorphism, which has been shown to influence prefrontal dopamine concentration, and the DRD2/ANKK1-Taq-Ia polymorphism, which has been related to the density of D2 receptors. Our results show that COMT effects on working memory performance are modulated by the DRD2/ANKK1-TAQ-Ia polymorphism and the specific working memory component process under investigation. Val, participants , supposedly characterized by increased prefrontal dopamine concentrations , outperformed Val+ participants in the manipulation of working memory contents, but only when D2 receptor density could be considered to be high. No such effect was present for passive maintenance of working memory contents or for maintenance in the face of distracting information. This beneficial effect of a balance between prefrontal dopamine availability and D2 receptor density reveals the importance of considering epistasis effects and different working memory subprocesses in genetic association studies. [source]

Dopamine gene predicts the brain's response to dopaminergic drug

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007
Michael X Cohen
Abstract Dopamine is critical for reward-based decision making, yet dopaminergic drugs can have opposite effects in different individuals. This apparent discrepancy can be accounted for by hypothesizing an ,inverted-U' relationship, whereby the effect of dopamine agents depends on baseline dopamine system functioning. Here, we used functional MRI to test the hypothesis that genetic variation in the expression of dopamine D2 receptors in the human brain predicts opposing dopaminergic drug effects during reversal learning. We scanned 22 subjects while they engaged in a feedback-based reversal learning task. Ten subjects had an allele on the Taq1A DRD2 gene, which is associated with reduced dopamine receptor concentration and decreased neural responses to rewards (A1+ subjects). Subjects were scanned twice, once on placebo and once on cabergoline, a D2 receptor agonist. Consistent with an inverted-U relationship between the DRD2 polymorphism and drug effects, cabergoline increased neural reward responses in the medial orbitofrontal cortex, cingulate cortex and striatum for A1+ subjects but decreased reward responses in these regions for A1, subjects. In contrast, cabergoline decreased task performance and fronto-striatal connectivity in A1+ subjects but had the opposite effect in A1, subjects. Further, the drug effect on functional connectivity predicted the drug effect on feedback-guided learning. Thus, individual variability in how dopaminergic drugs affect the brain reflects genetic disposition. These findings may help to explain the link between genetic disposition and risk for addictive disorders. [source]

Depression of retinogeniculate synaptic transmission by presynaptic D2 -like dopamine receptors in rat lateral geniculate nucleus

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006
G. Govindaiah
Abstract Extraretinal projections onto neurons in the dorsal lateral geniculate nucleus (dLGN) play an important role in modifying sensory information as it is relayed from the visual thalamus to neocortex. The dLGN receives dopaminergic innervation from the ventral tegmental area; however, the role of dopamine in synaptic transmission in dLGN has not been explored. In the present study, whole cell recordings were obtained to examine the actions of dopamine on glutamatergic synaptic transmission. Dopamine (2,100 µm) strongly suppressed excitatory synaptic transmission in dLGN relay neurons that was evoked by optic tract stimulation and mediated by both N -methyl- d -aspartate and non -N -methyl- d -aspartate glutamate receptors. In contrast, dopamine did not alter inhibitory synaptic transmission arising from either dLGN interneurons or thalamic reticular nucleus neurons. The suppressive action of dopamine on excitatory synaptic transmission was mimicked by the D2 -like dopamine receptor agonist bromocriptine (2,25 µm) but not by the D1 -like receptor agonist SKF38393 (10,25 µm). In addition, the dopamine-mediated suppression was antagonized by the D2 -like receptor antagonist sulpiride (10,20 µm) but not by the D1 -like receptor antagonist SCH23390 (5,25 µm). The dopamine-mediated decrease in evoked excitatory postsynaptic current amplitude was accompanied by an increase in the magnitude of paired-pulse depression. Furthermore, dopamine also reduced the frequency but not the amplitude of miniature excitatory postsynaptic currents. Taken together, these data suggest that dopamine may act presynaptically to regulate the release of glutamate at the retinogeniculate synapse and modify transmission of visual information in the dLGN. [source]

Extra-cellular dopamine increases in the paraventricular nucleus of male rats during sexual activity

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2003
Maria Rosaria Melis
Abstract Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations were measured in the dialysate obtained with vertical microdialysis probes implanted into the paraventricular nucleus of the hypothalamus of sexually potent male rats. Animals showed noncontact erections when put in the presence of, and copulated with a receptive (ovarietomized oestrogen and progesterone primed) female rat. Dopamine and DOPAC concentrations in the paraventricular dialysate increased 140% and 19%, respectively, above baseline values during exposure to the receptive female and 280% and 31%, respectively, during copulation. No changes in dopamine and DOPAC concentrations were detected in the paraventricular dialysate when sexually potent male rats were exposed to nonreceptive (ovariectomized not oestrogen plus progesterone primed) female rats. These results confirm the involvement of the paraventricular nucleus in control of erectile function and copulatory behaviour and show for the first time that dopamine neurotransmission is increased in this hypothalamic nucleus when erection occurs in physiological contexts. [source]

Dopamine gating of forebrain neural ensembles

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003
Patricio O'Donnell
Abstract Dopamine may exert different actions depending on a number of factors. A common view is that D1 receptors may be responsible for excitatory actions whereas D2 receptors are involved in inhibitory actions. However, this position cannot be reconciled with several findings indicating otherwise. The role of dopamine on forebrain neural ensembles may be better understood in the light of functional states of the system. Pyramidal cortical neurons and striatal medium spiny neurons alternate between two membrane potential states (,up' and ,down') that could shape dopamine actions. It is proposed that D1 receptors can act as state-stabilizers by sustaining up states and thereby facilitating plasticity mechanisms by providing postsynaptic depolarization and increasing NMDA function. In this way, dopamine can sustain activity in depolarized units. This action is accompanied by a decrease in cell firing (perhaps mediated by D2 receptors), which renders the cells responsive only to strong stimuli. The result would be a net increase in signal-to-noise ratio in a selected assembly of neurons. [source]

Mice transgenic for exon 1 of the Huntington's disease gene display reduced striatal sensitivity to neurotoxicity induced by dopamine and 6-hydroxydopamine

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001
Åsa Petersén
Abstract Huntington's disease is an autosomal dominant hereditary neurodegenerative disorder characterized by severe striatal cell loss. Dopamine (DA) has been suggested to play a role in the pathogenesis of the disease. We have previously reported that transgenic mice expressing exon 1 of the human Huntington gene (R6 lines) are resistant to quinolinic acid-induced striatal toxicity. In this study we show that with increasing age, R6/1 and R6/2 mice develop partial resistance to DA- and 6-hydroxydopamine-mediated toxicity in the striatum. Using electron microscopy, we found that the resistance is localized to the cell bodies and not to the neuropil. The reduction of dopamine and cAMP regulated phosphoprotein of a molecular weight of 32 kDa (DARPP-32) in R6/2 mice does not provide the resistance, as DA-induced striatal lesions are not reduced in size in DARPP-32 knockout mice. Neither DA receptor antagonists nor a N -methyl- d -aspartate (NMDA) receptor blocker reduce the size of DA-induced striatal lesions, suggesting that DA toxicity is not dependent upon DA- or NMDA receptor-mediated pathways. Moreover, superoxide dismutase-1 overexpression, monoamine oxidase inhibition and the treatment with the free radical scavenging spin-trap agent phenyl-butyl-tert-nitrone (PBN) also did not block DA toxicity. Levels of the antioxidant molecules, glutathione and ascorbate were not increased in R6/1 mice. Because damage to striatal neurons following intrastriatal injection of 6-hydroxydopamine was also reduced in R6 mice, a yet-to-be identified antioxidant mechanism may provide neuroprotection in these animals. We conclude that striatal neurons of R6 mice develop resistance to DA-induced toxicity with age. [source]

Effect of dopamine on rat diaphragm apoptosis and muscle performance

EXPERIMENTAL PHYSIOLOGY, Issue 4 2006
Janet D. Pierce
The purpose of this study was to determine whether dopamine (DA) decreases diaphragm apoptosis and attenuates the decline in diaphragmatic contractile performance associated with repetitive isometric contraction using an in vitro diaphragm preparation. Strenuous diaphragm contractions produce free radicals and muscle apoptosis. Dopamine is a free radical scavenger and, at higher concentrations, increases muscle contractility by simulating ,2 -adrenoreceptors. A total of 47 male Sprague,Dawley rats weighing 330,450 g were used in a prospective, randomized, controlled in vitro study. Following animal anaesthetization, diaphragms were excised, and muscle strips prepared and placed in a temperature-controlled isolated tissue bath containing Krebs,Ringer solution (KR) or KR plus 100 ,m DA. The solutions were equilibrated with oxygen (O2) at 10, 21 or 95% and 5% carbon dioxide, with the balance being nitrogen. Diaphragm isometric twitch and subtetanic contractions were measured intermittently over 65 min. The diaphragms were then removed and, using a nuclear differential dye uptake method, the percentages of normal, apoptotic and necrotic nuclei were determined using fluorescent microscopy. There were significantly fewer apoptotic nuclei in the DA group diaphragms than in the KR-only group diaphragms in 10 and 21% O2 following either twitch or subtetanic contractions. Dopamine at 100 ,m produced only modest increases in muscle performance in both 10 and 21% O2. The attenuation of apoptosis by DA was markedly greater than the effect of DA on muscle performance. Dopamine decreased diaphragmatic apoptosis, perhaps by preventing the activation of intricate apoptotic pathways, stimulating antiapoptotic mechanisms and/or scavenging free radicals. [source]

Dopamine, depression and antidepressants

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004
Eric Dailly
Abstract The relationship between depression and dopamine deficiency in the mesolimbic pathway has been hypothesized for many years. The experimental studies with animal models of depression and the human studies implicate the role of the dopamine system in depression. Not only do dopaminergic receptor agonists, but also antagonists such as olanzapine exhibit antidepressant effects associated with standard antidepressants in patients with treatment-resistant depression. This paradoxical result suggests that further investigations are necessary to understand the role played by dopamine in depression. [source]

One-Pot Preparation of Polymer,Enzyme,Metallic Nanoparticle Composite Films for High-Performance Biosensing of Glucose and Galactose

ADVANCED FUNCTIONAL MATERIALS, Issue 11 2009
Yingchun Fu
Abstract New polymer,enzyme,metallic nanoparticle composite films with a high-load and a high-activity of immobilized enzymes and obvious electrocatalysis/nano-enhancement effects for biosensing of glucose and galactose are designed and prepared by a one-pot chemical pre-synthesis/electropolymerization (CPSE) protocol. Dopamine (DA) as a reductant and a monomer, glucose oxidase (GOx) or galactose oxidase (GaOx) as the enzyme, and HAuCl4 or H2PtCl6 as an oxidant to trigger DA polymerization and the source of metallic nanoparticles, are mixed to yield polymeric bionanocomposites (PBNCs), which are then anchored on the electrode by electropolymerization of the remaining DA monomer. The prepared PBNC material has good biocompatibility, a highly uniform dispersion of the nanoparticles with a narrow size distribution, and high load/activity of the immobilized enzymes, as verified by transmission/scanning electron microscopy and electrochemical quartz crystal microbalance. The thus-prepared enzyme electrodes show a largely improved amperometric biosensing performance, e.g., a very high detection sensitivity (99 or 129,µA cm,2 mM,1 for glucose for Pt PBNCs on bare or platinized Au), a sub-micromolar limit of detection for glucose, and an excellent durability, in comparison with those based on conventional procedures. Also, the PBNC-based enzyme electrodes work well in the second-generation biosensing mode. The proposed one-pot CPSE protocol may be extended to the preparation of many other functionalized PBNCs for wide applications. [source]

Increased Dopamine Is Associated With the cGMP and Homocysteine Pathway in Female Migraineurs

HEADACHE, Issue 1 2010
Hans-Jürgen Gruber PhD
(Headache 2010;50:109-116) Background., The group of catecholamines, which include dopamine, adrenaline, and noradrenaline, are neurotransmitters which have been considered to play a role in the pathogenesis of migraine. However, the impact of catecholamines, especially dopamine on migraine as well as the exact mechanisms is not clear to date as previous studies have yielded in part conflicting results. Objective., This study aimed to produce a comprehensive examination of dopamine in migraineurs. Methods., Catecholamines and various parameters of the homocysteine, folate, and iron metabolism as well as cyclic guanosine monophosphate (cGMP) and inflammatory markers were determined in 135 subjects. Results., We found increased dopamine levels in the headache free period in female migraineurs but not in male patients. Increased dopamine is associated with a 3.30-fold higher risk for migraine in women. We found no significant effects of aura symptoms or menstrual cycle phases on dopamine levels. Dopamine is strongly correlated with cGMP and the homocysteine,folate pathway. Conclusion., We show here that female migraineurs exhibit increased dopamine levels in the headache free period which are associated with a higher risk for migraine. [source]

Relations of clinical features, subgroups and medication to serum monoamines in schizophrenia

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2002
Robert D. Oades
Abstract Background Plasma and serum indices of monoaminergic activity reflect partly the illness of schizophrenia (e.g. HVA/deficit syndrome) and sometimes the symptoms (e.g. HVA/anhedonia). But, such studies have rarely taken both metabolites and parent amines or inter-amine activity ratios into account. We hypothesized that comparing the major symptom dimensions to measures of transmitter activity (with and without control for antipsychotic drug treatment) would show differential patterns of activity useful for the design of pharmacological treatments. Methods Dopamine (DA), noradrenaline (NA), serotonin (5-HT), their three major metabolites and prolactin were measured in the serum of 108 patients with schizophrenia and 63 matched controls: DA D2-receptor blocking-activity was estimated from a regression of butyrophenone displacement in striatum in vitro on to PET reports of drug-binding in vivo. Symptoms were factored into four dimensions (disorganized/thought disorder, nonparanoid/negative, ideas-of-reference and paranoid/positive symptoms). Results (1) Patients' DA activity did not differ from controls: but their 5-HT and NA turnovers increased/decreased, respectively, and the DA/5HT-metabolite ratio was lower. Increased DA-D2-receptor occupancy was predicted by decreased DA-metabolism and its ratio to 5-HT-metabolism. (2) Patients had higher levels of NA, DA-metabolites and DA-/5-HT-metabolite ratios on atypical vs typical drugs. (3) Increased D2-occupancy was associated with lower DA metabolism in paranoid patients but was unrelated to relative increases of DA/5-HT- and NA-metabolism in nonparanoid patients. (4) Low DA-/5-HT-metabolite ratios, high prolactin and low DA-metabolism characterized thought-disordered patients. (5) High DA-/5-HT-metabolite ratios paralleled many ideas-of-reference. The metabolites were sensitive, respectively, to control for D2-occupancy and prolactin. Conclusions The role of DA in paranoid, and 5-HT in thought-disordered and ideas-of-reference dimensions point both to the mechanisms underlying the features typical of these subgroups and the type of medication appropriate. Copyright © 2002 John Wiley & Sons, Ltd. [source]